PROJECT SUMMARY The molecular signaling pathways important to speech and language remain mostly unknown. FoxP2 is one of a few genes that has been directly linked to both speech and language in humans and learning and production of vocalizations in animal models (songbirds and mice). In humans and songbirds, striatal expression of FoxP2 is a key factor in the accurate development of learned vocalizations. This multi-PI grant will synthesize expertise in genomics and behavior to examine the role of FoxP2 during the sensitive period for vocal learning. We will examine the function of FoxP2 during vocal learning, and in adult animals, using a combination of novel viral methods for the reversible knockdown of FoxP2, and functional genomics, through two specific aims. In the first aim, we will use novel viral methods to test whether restoring normal FoxP2 expression levels in adults is sufficient to rescue vocal deficits caused by knockdown of FoxP2 expression during the sensitive period for vocal learning. In the second aim, we will use functional genomics to identify the expression and regulation of FoxP2 target genes during the sensitive period for vocal learning. The results of these studies will provide new insights into neurodevelopmental genetic disorders, including the identification of novel signaling pathways involved in learning of vocal behaviors, and how therapeutic intervention in adults can impact behavioral disorders acquired during developmental sensitive periods. These data can also be used for the future development of targeted therapeutics for the treatment of a range of neurodevelopmental disorders with speech and language phenotypes.